The overall aims of this project are to study the molecular biology of the malarial parasite, Plasmodium. In particular, to study the regulation of the major surface antigen of the P. knowlesi sporozoites (CS-gene), and to discover the molecular basis of its stage specific expression. Such structures are important for two reasons: First, it is already apparent that the molecular biology of Plasmodia is unusual and the molecular mechanisms controlling its development and gene expression of may throw a unique light on higher organism development. Secondly, any understanding of Plasmodia molecular biology may well be relevant to curing Malaria, the world's most prevalent infectious disease. To this end, the regulatory sequences of the CS-gene transcription unit will be identified, by both nucleotide sequencing and mutagenic studies. (2) The role of DNA transposition and amplification in CS-gene stage specific expression will be investigated. (3) Heterologous non-parasite systems will be developed in which regulation of cloned Plasmodium genescan be studied. (4) Selectable vectors and a gene transfer system will be developed for P. falciparum in vitro grown blood form parasites and (5) a search will be made for other Plasmodium genes containing long tandemly repeated internal units within their coding sequences.